Circ_0007429/miR-637/TRIM71/Ago2 axis participates in the regulation of proliferation, migration, invasion, apoptosis, and aerobic glycolysis of HCC.

CircRNAs play an important role in the progression of hepatocellular carcinoma (HCC), however, the role of circ_0007429 in HCC remains unknown. Using bioinformatics tools, we selected circ_0007429 that was most highly expressed in HCC tissues and investigated its role in HCC progression. Immunohistochemistry, plasmid transfection, real-time quantitative PCR, and western blot analysis were used to identify the relationship between circ_0007429 and its potential target, miR-637, and TRIM71. The regulatory effect of circ_0007429 on miR-637/TRIM71/Ago2 signaling and its key role in HCC progression were studied in vitro. A nude mouse xenograft model was used to examine tumor growth in vivo. Circ_0007429 and TRIM71 expression were upregulated, while miR-637 expression was downregulated in HCC tissues and cells compared with their expression in control groups. Knockdown of circ_0007429 enhanced apoptosis in HCC cells, while impeded proliferation, migration, invasion, and aerobic glycolysis, which were reversed by miR-637 inhibitor. High levels of circ_0007429 correlated with a poor survival rate of HCC patients. Additionally, circ_0007429 interfering inhibited tumor growth in vivo. TRIM71 directly bound to miR-637 and inhibited Ago2 expression. Moreover, circ_0007429 promotes aerobic glycolysis in HCC cells through the miR/TRIM71/Ago2 axis. Circ_0007429 promotes HCC progression by promoting cell proliferation, migration, invasion, and aerobic glycolysis and by inhibiting cell apoptosis through the miR/TRIM71/Ago2 axis. These results provide molecular insights into the mechanism of HCC and suggest that circ_0007429 could be a therapeutic target for HCC.

Parametric multiphysics study of focus-variable silicone lenses.

By exploiting their inherent elasticity, focus-variable silicone lenses shift their focal length reversibly when deformed. Although biconcave and meniscus lenses contribute to optical systems just as well as biconvex lenses, studies primarily revolve around the latter. Thus, we aim to reveal the focal length shifting potential of all aforementioned lens types. Covering a wide parameter range of varying lens curvature radii, we present a coupled mechanical and optical simulation in which a lens deformation is applied. The results show significant differences in focal length shifting effectiveness for different lens types. Within the domains of specific lens types, trends in this effectiveness emerge for different combinations of curvature radii. Matching these radii when incorporating adaptive silicone lenses in optical systems may guide optics engineers toward more effective system designs through this study.

AMPK: The key to ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) refers to a syndrome in which tissue damage is further aggravated and organ function further deteriorates when blood flow is restored after a period of tissue ischemia. Acute myocardial infarction, stress ulcer, pancreatitis, intestinal ischemia, intermittent claudication, acute tubular necrosis, postshock liver failure, and multisystem organ failure are all related to reperfusion injury. AMP-activated protein kinase (AMPK) has been identified in multiple catabolic and anabolic signaling pathways. The functions of AMPK during health and diseases are intriguing but still need further research. Except for its conventional roles as an intracellular energy switch, emerging evidence reveals the critical role of AMPK in IRI as an energy-sensing signal molecule by regulating metabolism, autophagy, oxidative stress, inflammation, and other progressions. At the same time, drugs based on AMPK for the treatment of IRI are constantly being researched and applied in clinics. In this review, we summarize the mechanisms underlying the effects of AMPK in IRI and describe the AMPK-targeting drugs in treatment, hoping to increase the understanding of AMPK in IRI and provide new insights into future clinical treatment.

Research progress on ncRNAs regulation of mitochondrial dynamics in diabetes.

Diabetes mellitus and its complications are major health concerns worldwide that should be routinely monitored for evaluating disease progression. And there is currently much evidence to suggest a critical role for mitochondria in the common pathogenesis of diabetes and its complications. Mitochondrial dynamics are involved in the development of diabetes through mediating insulin signaling and insulin resistance, and in the development of diabetes and its complications through mediating endothelial impairment and other closely related pathophysiological mechanisms of diabetic cardiomyopathy (DCM). noncoding RNAs (ncRNAs) are closely linked to mitochondrial dynamics by regulating the expression of mitochondrial dynamic-associated proteins, or by regulating key proteins in related signaling pathways. Therefore, this review summarizes the research progress on the regulation of Mitochondrial Dynamics by ncRNAs in diabetes and its complications, which is a promising area for future antibodies or targeted drug development.

Molecular epidemiology, phenotypic and genomic characterization of antibiotic-resistant enterococcal isolates from diverse farm animals in Xinjiang, China.

Multidrug-resistant (MDR) bacteria in farm environments can be transferred to humans through the food chain and occupational exposure. Enterococcus infections caused by linezolid resistant enterococci (LRE) are becoming more challenging to treat as their resistance to antibiotics intensifies. Therefore, this study investigated the molecular epidemiology, phenotypic and genomic characterization of enterococci in seven species of farm animals (sheep, chicken, swine, camel, cattle, equine, pigeon) anal swab from Xinjiang, China by agar dilution method, polymerase chain reaction (PCR), whole-genome sequencing (WGS) and bioinformatics analysis. A total of 771 samples were collected, 599 (78 %) were contaminated with Enterococcus spp., among which Enterococcus faecalis (350/599) was dominant. Antimicrobial susceptibility testing showed that high resistance was observed in rifampicin (80 %), tetracycline (71 %), doxycycline (71 %), and erythromycin (69 %). The results of PCR showed the highest prevalent antibiotic resistance genes (ARGs) were aac(6')-aph(2″) (85 %), followed by tet(M) (73 %), erm(B) (62 %), and aph(3')-IIIa (61 %). Besides, 29 optrA-carrying E. faecalis isolates belonging to 13 STs (including 3 new alleles) were detected, with ST714 (31 %, 9/29) being the dominant ST type. The phylogenetic tree showed that optrA-carrying E. faecalis prevalent in the intensive swine farm is mainly caused by clonal transmission. Notably, optrA gene in Enterococcus spp. isolate from camel was first characterized here. WGS of E. faecalis F109 isolate from camel confirmed the colocalization of optrA with other five ARGs in the same plasmid (pAFL-109F). The optrA-harboring genetic context is IS1216E-fexA-optrA-erm(A)-IS1216E. This study highlights the prevalence of MDR Enterococcus (≥88 %) and four ARGs (≥75 %) in swine (intensive farming), cattle (commercial farming), and chickens (backyard farming) are high and also highlights that optrA-carrying E. faecalis of farm animals incur a transmission risk to humans through environment, food consumption and others. Therefore, antibiotic-resistant bacteria (ARB) monitoring and effective control measures should be strengthened and implemented in diverse animals.

The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis.

Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the molecular biological mechanisms of bone remodeling, they have come to realize the crucial role of posttranscriptional gene control in bone metabolism homeostasis. RNA-binding proteins, as essential actors in posttranscriptional activities, may exert influence on osteoporosis progression by regulating the RNA life cycle. This review compiles recent findings on the involvement of RNA-binding proteins in abnormal bone metabolism in osteoporosis and describes the impact of some key RNA-binding proteins on bone metabolism regulation. Additionally, we explore the potential and rationale for modulating RNA-binding proteins as a means of treating osteoporosis, with an overview of drugs that target these proteins.

Pioglitazone ameliorates ischemia/reperfusion-induced acute kidney injury via oxidative stress attenuation and NLRP3 inflammasome.

Acute kidney injury (AKI) induced by renal ischemia/reperfusion injury (IRI) is a severe clinical condition. ROS accumulation, antioxidant pathways deficiency, and inflammation are involved in IRI. Pioglitazone (Pio) exerts anti-inflammatory and antioxidant effects. The aim of this study was to explore the protective effects of pioglitazone against IRI-induced AKI. Pathogen-free Sprague-Dawley (SD) rats were arbitrarily divided into four groups: Sham operation group Control (CON) group, CON + Pio group, I/R + Saline group, and I/R + Pio group. In addition, HK-2 cells were subjected to hypoxia and reoxygenation to develop an H/R model for investigation of the protective mechanism of Pio. Pretreatment with pioglitazone in the model rats reduced urea nitrogen and creatinine levels, histopathological scores, and cytotoxicity after IRI. Pioglitazone treatment significantly attenuated renal cell apoptosis, decreased cytotoxicity, increased Bcl-2 expression, and downregulated Bax expression. Besides, the levels of ROS and inflammatory factors, including NLRP3, ASC, pro-IL-1ß, pro-caspase-1, cleaved-caspase-1, TNF-α, IL-6, and IL-1ß, in I/R rats and H/R cells were normalized by the pioglitazone treatment. Pioglitazone improved IRI-induced AKI by attenuating oxidative stress and NLRP3 inflammasome activation. Therefore, pioglitazone has the potential to serve as a novel agent for renal IRI treatment and prevention.

Development of a multiparametric model for predicting the response to neoadjuvant chemotherapy in breast cancer.

Background: Choosing the appropriate treatment early and predicting the efficacy of neoadjuvant chemotherapy (NAC) for locally advanced breast cancer patients are of particular importance for clinicians. Developing and validating a multiparametric model for predicting NAC would be very meaningful for clinical practice. Methods: This study included 91 patients with locally advanced breast cancer treated from 2016 to 2020. The correlation between multiparametric characteristics and the efficacy of NAC was examined. The data were randomly divided into training and validation sets. A least absolute shrinkage and selection operator (LASSO) regression analysis was used for the variable screening. A multivariable logistic regression analysis was used to construct the model. Calibration and decision curves were used to assess the performance of the established model. Results: Lymph node metastasis, the first standard apparent diffusion coefficient (ADC) at the baseline, the change in the standard ADC at the first follow-up, the change in tumor volume at the first follow-up, and the clinical stage of the tumor at the baseline were selected for inclusion in the model. In the receiver operating characteristic (ROC) analysis, the areas under the curve (AUCs) were 0.984 [95% confidence interval (CI): 0.958-1] and 0.815 (95% CI: 0.509-1) for the primary and validation cohorts, respectively. The utility of the established model was confirmed by calibration and decision curves, and a nomogram was obtained. Conclusions: A multiparametric model based on clinical-pathological-magnetic resonance imaging (MRI) features was established to predict the effect of NAC in patients with locally advanced breast cancer.

Study on the spatio-temporal evolution and influencing factors of farmland abandonment on a county scale.

The protection of farmland resources is related to world food security, as well as the smooth realization of the goals of UN 2030 Agenda for Sustainable Development and China's Rural Revitalization Plan. As the most active region in the global economic development and one of the main grain producing areas, the problem of farmland abandonment in the Yangtze River Delta gradually appears with the rapid development of urbanization. Therefore, based on the interpretation data of remote sensing images and field survey data of three periods in 2000, 2010, and 2018, this study used Moran's I and geographical barycenter model to reveal the spatiotemporal evolution law of farmland abandonment in Pingyang County of the Yangtze River Delta. And then, this study selected 10 indicators covering four categories: geography, proximity, distance, and policy, and used random forest model to reveal the main influencing factors of farmland abandonment in the study area. The results showed that the abandoned farmland increased from 441.58 hm2 in 2000 to 5797.40 hm2 in 2018. The hot spot and barycenter of land abandonment gradually shifted from the western mountainous areas to the eastern plain areas. Altitude and slope were the main factors affecting the farmland abandonment. The high the altitude and the great the slope, the farmland abandonment in mountainous areas were serious. The proximity factors had a greater impact on the expansion of farmland abandonment from 2000 to 2010, and then the impact weakened. In view of the above analysis, the countermeasures and suggestions for maintaining food security were finally put forward.

Cost-effectiveness of palbociclib plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer - A Chinese healthcare system perspective.

Aim: To evaluate the cost-effectiveness of palbociclib plus fulvestrant in the second-line treatment of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative advanced breast cancer based on the latest published follow-up data from the perspective of the Chinese healthcare system. Methods: In view of the PALOMA-3 trial, a Markov model was built for this purpose, which included three health states: progression-free survival (PFS), progressed disease (PD), and death. The cost and health utilities were mainly derived from the published literature. One-way sensitivity analysis and probabilistic sensitivity analysis were carried out to verify the robustness of the model. Results: In the base case analysis, compared with the placebo plus fulvestrant arm, the palbociclib plus fulvestrant arm yielded an additional 0.65 quality-adjusted life years (QALYs) (2.56 QALYs vs. 1.90 QALYs) with an incremental cost of $36,139.94 ($55,482.06 vs. $19,342.12), resulting an incremental cost-effectiveness ratio (ICER) of $55,224.90/QALY, which was deeply higher than a willingness-to-pay (WTP) threshold of $34,138.28 per QALY in China. The results of one-way sensitivity analysis indicated that the utility of PFS, cost of palbociclib, and cost of neutropenia had a great influence on the ICER. Conclusions: Palbociclib plus fulvestrant is unlikely to be cost-effective in comparison with placebo plus fulvestrant as second-line therapy of women with HR+/HER2- advanced breast cancer.

RNA-binding proteins in metabolic-associated fatty liver disease (MAFLD): From mechanism to therapy.

Metabolic-associated fatty liver disease (MAFLD) is the most common chronic liver disease globally and seriously increases the public health burden, affecting approximately one quarter of the world population. Recently, RNA binding proteins (RBPs)-related pathogenesis of MAFLD has received increasing attention. RBPs, vividly called the gate keepers of MAFLD, play an important role in the development of MAFLD through transcription regulation, alternative splicing, alternative polyadenylation, stability and subcellular localization. In this review, we describe the mechanisms of different RBPs in the occurrence and development of MAFLD, as well as list some drugs that can improve MAFLD by targeting RBPs. Considering the important role of RBPs in the development of MAFLD, elucidating the RNA regulatory networks involved in RBPs will facilitate the design of new drugs and biomarkers discovery.

Regulation of NcRNA-protein binding in diabetic foot.

Non-coding RNA (ncRNA) is a special type of RNA transcript that makes up more than 90 % of the human genome. Although ncRNA typically does not encode proteins, it indirectly controls a wide range of biological processes, including cellular metabolism, development, proliferation, transcription, and post-transcriptional modification. NcRNAs include small interfering RNA (siRNA), PIWI-interacting RNA (piRNA), tRNA-derived small RNA (tsRNA), etc. The most researched of these are miRNA, lncRNA, and circRNA, which are crucial regulators in the onset of diabetes and the development of associated consequences. The ncRNAs indicated above are linked to numerous diabetes problems by binding proteins, including diabetic foot (DF), diabetic nephropathy, diabetic cardiomyopathy, and diabetic peripheral neuropathy. According to recent studies, Mir-146a can control the AKAP12 axis to promote the proliferation and migration of diabetic foot ulcer (DFU) cells, while lncRNA GAS5 can activate HIF1A/VEGF pathway by binding to TAF15 to promote DFU wound healing. However, there are still many unanswered questions about the mechanism of action of ncRNAs. In this study, we explored the mechanism and new progress of ncRNA-protein binding in DF, which can provide help and guidance for the application of ncRNA in the early diagnosis and potential targeted intervention of DFU.

Polysaccharides-based nanocarriers enhance the anti-inflammatory effect of curcumin.

Curcumin (CUR) has been discovered to have many biological activities, including anti-inflammatory, anti-cancer, anti-oxygenation, anti-human immunodeficiency virus, anti-microbial and exhibits a good effect on the prevention and treatment of many diseases. However, the limited properties of CUR, including the poor solubility, bioavailability and instability caused by enzymes, light, metal irons, and oxygen, have compelled researchers to turn their attention to drug carrier application to overcome these drawbacks. Encapsulation may provide potential protective effects to the embedding materials and/or have a synergistic effect with them. Therefore, nanocarriers, especially polysaccharides-based nanocarriers, have been developed in many studies to enhance the anti-inflammatory capacity of CUR. Consequently, it's critical to review current advancements in the encapsulation of CUR using polysaccharides-based nanocarriers, as well as further study the potential mechanisms of action where polysaccharides-based CUR nanoparticles (the complex nanoparticles/Nano CUR-delivery systems) exhibit their anti-inflammatory effects. This work suggests that polysaccharides-based nanocarriers will be a thriving field in the treatment of inflammation and inflammation-related diseases.

Multifaceted roles of T cells in obesity and obesity-related complications: A narrative review.

Obesity is characterized by chronic low-grade inflammatory responses in the adipose tissue, accompanied by pronounced insulin resistance and metabolic anomalies. It affects almost all body organs and eventually leads to diseases such as fatty liver disease, type 2 diabetes mellitus, and atherosclerosis. Recently, T cells have emerged as interesting therapeutic targets because the dysfunction of T cells and their cytokines in the adipose tissue is implicated in obesity-induced inflammation and their complicated onset. Although several recent narrative reviews have provided a brief overview of related evidence in this area, they have mainly focused on either obesity-associated T cell metabolism or modulation of T cell activation in obesity. Moreover, at present, no published review has reported on the multifaceted roles of T cells in obesity and obesity-related complications, even though there has been a significant increase in studies on this topic since 2019. Therefore, this narrative review aims to comprehensively summarize current advances in the mechanistic roles of T cells in the development of obesity and its related complications. Further, we aim to discuss relevant drugs for weight loss as well as the contradictory role of T cells in the same disease so as to highlight key findings regarding this topic and provide a valid basis for future treatment strategies.

Insights into monkeypox pathophysiology, global prevalence, clinical manifestation and treatments.

On 23rd July 2022, the World Health Organization (WHO) recognized the ongoing monkeypox outbreak as a public medical crisis. Monkeypox virus (MPV), the etiological agent of monkeypox, is a zoonotic, linear, double-stranded DNA virus. In 1970, the Democratic Republic of the Congo reported the first case of MPV infection. Human-to-human transmission can happen through sexual contact, inhaled droplets, or skin-to-skin contact. Once inoculated, the viruses multiply rapidly and spread into the bloodstream to cause viremia, which then affect multiple organs, including the skin, gastrointestinal tract, genitals, lungs, and liver. By September 9, 2022, more than 57,000 cases had been reported in 103 locations, especially in Europe and the United States. Infected patients are characterized by physical symptoms such as red rash, fatigue, backache, muscle aches, headache, and fever. A variety of medical strategies are available for orthopoxviruses, including monkeypox. Monkeypox prevention following the smallpox vaccine has shown up to 85% efficacy, and several antiviral drugs, such as Cidofovir and Brincidofovir, may slow the viral spread. In this article, we review the origin, pathophysiology, global epidemiology, clinical manifestation, and possible treatments of MPV to prevent the propagation of the virus and provide cues to generate specific drugs.

Identification of necroptosis-related features in diabetic nephropathy and analysis of their immune microenvironent and inflammatory response.

Background: Diabetic nephropathy (DN) was considered a severe microvascular complication of diabetes, which was recognized as the second leading cause of end-stage renal diseases. Therefore, identifying several effective biomarkers and models to diagnosis and subtype DN is imminent. Necroptosis, a distinct form of programmed cell death, has been established to play a critical role in various inflammatory diseases. Herein, we described the novel landscape of necroptosis in DN and exploit a powerful necroptosis-mediated model for the diagnosis of DN. Methods: We obtained three datasets (GSE96804, GSE30122, and GSE30528) from the Gene Expression Omnibus (GEO) database and necroptosis-related genes (NRGs) from the GeneCards website. Via differential expression analysis and machine learning, significant NRGs were identified. And different necroptosis-related DN subtypes were divided using consensus cluster analysis. The principal component analysis (PCA) algorithm was utilized to calculate the necroptosis score. Finally, the logistic multivariate analysis were performed to construct the necroptosis-mediated diagnostic model for DN. Results: According to several public transcriptomic datasets in GEO, we obtained eight significant necroptosis-related regulators in the occurrence and progress of DN, including CFLAR, FMR1, GSDMD, IKBKB, MAP3K7, NFKBIA, PTGES3, and SFTPA1 via diversified machine learning methods. Subsequently, employing consensus cluster analysis and PCA algorithm, the DN samples in our training set were stratified into two diverse necroptosis-related subtypes based on our eight regulators' expression levels. These subtypes exhibited varying necroptosis scores. Then, we used various functional enrichment analysis and immune infiltration analysis to explore the biological background, immune landscape and inflammatory status of the above subtypes. Finally, a necroptosis-mediated diagnostic model was exploited based on the two subtypes and validated in several external verification datasets. Moreover, the expression level of our eight regulators were verified in the singe-cell level and glomerulus samples. And we further explored the relationship between the expression of eight regulators and the kidney function of DN. Conclusion: In summary, our necroptosis scoring model and necroptosis-mediated diagnostic model fill in the blank of the relationship between necroptosis and DN in the field of bioinformatics, which may provide novel diagnostic insights and therapy strategies for DN.

Case report: Takotsubo syndrome induced by severe hypoglycemia.

Background: Takotsubo syndrome (TTS) is a disorder frequently characterized by transient dysfunction of the apical portion of the left ventricle with hyperkinesis in other parts of the heart walls. TTS is also called stress cardiomyopathy because it is known to be triggered by emotional or physical stress. We report a case of TTS associated with severe hypoglycemia. Case summary: An 85-year-old female patient with a history of non-insulin-dependent diabetes mellitus and hypertension presented to the emergency department with hypoglycemia-induced unconsciousness. The patient regained consciousness after an intravenous glucose injection. The patient complained of chest discomfort after the correction of hypoglycemia. Electrocardiography (ECG) revealed ST-segment elevation in leads V2-V5, therefore, ST-segment elevation myocardial infarction was highly suspected. Echocardiography showed impaired left ventricular systolic function with an ejection fraction of 40% accompanied by hypokinesis of the apex. Percutaneous coronary angiography showed 30% stenosis of the left anterior descending coronary artery. Left ventricular angiography revealed apical dyskinesia, which is typical of the classic apical ballooning shape of takotsubo. The patient was diagnosed with TTS and managed with pharmacological therapy, including antiplatelet (i.e., aspirin), lipid-lowering, anti-heart failure, and hypoglycemic drugs. The patient was successfully discharged in a stable condition. Conclusion: This is a representative case of TTS caused by hypoglycemia. Due to the self-limiting nature of TTS, diagnoses can be missed among hypoglycemic patients. Thus, echocardiography is required for patients with hypoglycemia to ensure an accurate TTS diagnosis in the emergency department.

The Regulatory Role of MicroRNAs on Phagocytes: A Potential Therapeutic Target for Chronic Diseases.

An effective acute inflammatory response results in the elimination of infectious microorganisms, followed by a smooth transition to resolution and repair. During the inflammatory response, neutrophils play a crucial role in antimicrobial defense as the first cells to reach the site of infection damage. However, if the neutrophils that have performed the bactericidal effect are not removed in time, the inflammatory response will not be able to subside. Anti-inflammatory macrophages are the main scavengers of neutrophils and can promote inflammation towards resolution. MicroRNAs (miRNAs) have great potential as clinical targeted therapy and have attracted much attention in recent years. This paper summarizes the involvement of miRNAs in the process of chronic diseases such as atherosclerosis, rheumatoid arthritis and systemic lupus erythematosus by regulating lipid metabolism, cytokine secretion, inflammatory factor synthesis and tissue repair in two types of cells. This will provide a certain reference for miRNA-targeted treatment of chronic diseases.

Puerarin protects against sepsis-induced myocardial injury through AMPK-mediated ferroptosis signaling.

OBJECTIVE: Research suggests that Puerarin may protect against sepsis-induced myocardial damage. However, the mechanisms responsible for Puerarin's cardioprotective effect remain largely unclear. In this study, our objective is to investigate the role of Puerarin-induced AMPK-mediated ferroptosis signaling in protecting myocardial injury. METHODS: 48 male Sprague-Dawley rats were randomly divided into four groups: control group, LPS group, LPS + Pue group, LPS + Pue + Era (Erastin, ferroptosis activator) group, or LPS + Pue + CC (compound C, AMPK inhibitor) group. During the experiment, cardiac systolic function indexes and myocardial histopathological changes were monitored. The serum levels of myocardial injury marker enzyme, inflammatory response related marker enzyme, and oxidative stress related-marker enzyme were measured with ELISA. Apoptotic cardiomyocytes, the iron content in myocardial tissue, apoptosis-related proteins, AMPK, and ferroptosis-related proteins were determined. RESULTS: Puerarin inhibited the myocardial injury induced by LPS. The cardioprotective effects of Puerarin decreased after adding ferroptosis-activating compound Erastin. The protein expression levels of GPX4 and ferritin were down-regulated, whereas ACSL4, TFR, and heart iron content were up-regulated in LPS + Pue + Era group compared with LPS+Pue group. A significant difference was identified between LPS + Pue + Era group and LPS + Pue group in P-AMPK and T-AMPK levels. Meanwhile, after providing CC, P-AMPK/T-AMPK was significantly reduced, the protein expression levels of GPX4 and ferritin were down-regulated. ACSL4, TFR, and the heart iron content were up-regulated in LPS + Pue + CC group compared to LPS + Pue group. CONCLUSIONS: Puerarin protected against sepsis-induced myocardial injury, and AMPK-mediated ferroptosis signaling played a crucial role in its cardioprotective effect.

Ferroptosis and ferritinophagy in diabetes complications.

BACKGROUND: With long-term metabolic malfunction, diabetes can cause serious damage to whole-body tissue and organs, resulting in a variety of complications. Therefore, it is particularly important to further explore the pathogenesis of diabetes complications and develop drugs for prevention and treatment. In recent years, different from apoptosis and necrosis, ferroptosis has been recognized as a new regulatory mode of cell death and involves the regulation of nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy. Evidence shows that ferroptosis and ferritinophagy play a significant role in the occurrence and development of diabetes complications. SCOPE OF REVIEW: we systematically review the current understanding of ferroptosis and ferritinophagy, focusing on their potential mechanisms, connection, and regulation, discuss their involvement in diabetes complications, and consider emerging therapeutic opportunities and the associated challenges with future prospects. MAJOR CONCLUSIONS: In summary, ferroptosis and ferritinophagy are worthy targets for the treatment of diabetes complications, but their complete molecular mechanism and pathophysiological process still require further study.